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Method of analysis of amine by mass spectrometry

a mass spectrometry and amine technology, applied in the field of quantitative analysis of amines, can solve the problems of high cost of synthesis of stable isotope internal standards, limited choice of appropriate labeled reagents for chemical synthesis of stable isotope labeled internal standards,

Inactive Publication Date: 2007-01-11
NGUYEN HOA DUC +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This approach enables rapid, reliable, and cost-effective synthesis of stable isotope labeled internal standards, facilitating high-throughput analysis of amines by isotope dilution mass spectrometry with improved precision and accuracy, suitable for both individual and library analyses.

Problems solved by technology

These criteria of an ideal stable isotope labeled internal standard present a challenge for organic synthesis chemists who help the analytical chemists in the analysis.
Even though many stable isotope labeled reagents are commercially available, the choice of appropriate labeled reagent for chemical synthesis of stable isotope labeled internal standards is still very limited.
The limited isotope labeled reagents and the multi-step synthesis contribute to the high cost of synthesis of stable isotope internal standards.
Even if the analytical chemist who carries out the analysis can afford the cost of the synthesis, there is also a time factor that he or she has to consider before ordering the synthesis.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example

Analysis of Paroxetin in Human Serum Plasma

Step 1: Preparation of N-Acetylparoxetin-d3.

[0024] A solution of 10 mg of paroxetin in ethyl acetate was treated with 2 equivalents of acetic anhydride-d6. The resulting solution was stirred for an hour then was quenched with aqueous sodium carbonate. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried with magnesium sulfate. The filtered solution was concentrated and the residue was purified by column chromatography using silica gel as absorbant and methanol-chloroform mixture as eluant. The fractions containing clean N-acetylparoxetin-d3 were combined and concentrated to give 4 mg product as a white solid. MS analysis gave MH+375.

Step 2: Preparation of Working Standard Solutions and Internal Standard Solution.

[0025] Working standard solutions of Paroxetin were prepared by weighing paroxetin and diluting the stock solution to appropriate concentration as follows:

SolutionA0.1ug / ml in ethyl a...

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Abstract

Method of identification and quantitative analysis of primary and / or secondary amine(s) in a sample by mass spectrometry using stable isotope labeled internal standard is provided. Said internal standard is prepared by reaction of an authentic sample of said amine with a stable isotope labeled reagent, and is added to a sample containing said amine. Said amine in said sample is then quantitatively converted to a chemical compound of identical structure, except the stable isotope atoms, as that of said internal standard using a non-labeled reagent. Said sample is then extracted and the extract is analyzed by mass spectrometry. Identification and quantification of said amine are made from a plot of ion ratio of said converted amine to said internal standard versus amine concentration.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] Not applicable STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] Not applicable BACKGROUND OF THE INVENTION [0003] This invention pertains to methods of quantitative analysis of amines in a sample by isotope dilution mass spectrometry. The stable isotope labeled amides are used as internal standards. The sample may be a biological fluid, such as serum, urine etc., or an aqueous sample such as an environmental or an agricultural sample. [0004] While various methods of analysis such as immunoassays and chromatographic analysis—LC (liquid chromatography), GC (gas chromatography), and TLC (thin layer chromatography)—have been reported for identification and determination of levels of amines in analytical samples, the absolute and unequivocal identification and quantitative analysis of those compounds are combinations of chromatographic analysis and MS (mass spectrometry) such as GC-MS and LC-MS. The accuracy and precisi...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G01N33/00A61M36/14G01N33/487
CPCG01N33/6848Y10T436/17Y10T436/173845H01J49/00
Inventor NGUYEN, HOA DUCNGUYEN, TRINH DUCNGUYEN, DUC TIEN
Owner NGUYEN HOA DUC
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